- 77 Elektronika Kft.
- Issuing Office:
- Center for Devices and Radiological Health
| || |
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
| || 0903 New Hampshire Avenue|
Silver Spring, MD 20993
OCT 8, 2015
VIA UNITED PARCEL SERVICE
77 Elektronika Kft.
Fehervari ut 98
Dear Mr. Zettwitz:
During an inspection of your firm located in Budapest, Hungary on March 9, 2015 through March 12, 2015, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Urisys 1100 Urine Analyzer. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.
We received a response from Mr. Rudolf Tolgyesi, Quality Assurance Director, dated April 2, 2015 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a).
For example, your firm has not validated the processes used in the manufacture of Urisys 1100, a Class II medical device, according to an established procedure. Specifically:
a. Your firm did not validate the (b)(4) used in the manufacture of critical components for Urisys 1100. Your firm only documented a '(b)(4)' for the processes. Your firm’s master validation plan does not include (b)(4). During the inspection, Mr. Rudolf Tolgyesi, QA Director, stated that your firm has not conducted validation for (b)(4) processes.
b. Your firm has not validated (b)(4) used in the manufacture of the Urisys 1100. Your firm's qualification of the (b)(4) process was inadequate. Specifically, review of the protocol and validation report for (b)(4) showed that your firm did not check for the variation (b)(4). In addition, your firm did not provide objective evidence that it validated (b)(4), correctly placed components, or all (b)(4). The protocols did not identify any acceptance criteria or a worst case scenario.
We reviewed your firm’s response and conclude that it is not adequate. Your firm stated that although validation was not performed (b)(4) the Urisys 1100 analyzers undergo 100% functional testing. Your firm has undertaken the following corrections and corrective actions:
i. Opened CAPA 2015-037 for this observation.
ii. Plans to revise (b)(4) Qualification Procedure to address all 21 CFR 820 requirements, and include validation testing protocols and practical aspects of validation to work instructions for (b)(4). Your firm plans to complete the revision by May 15, 2015.
iii. Plans to validate the (b)(4) and (b)(4) by September 30, 2015.
iv. Plans to update the Master Validation Plan, if needed, based on the revised (b)(4) Procedure. In addition, all existing process validation documentation for Urisys1100 and check validation documentation will be reviewed to determine if they meet revised (b)(4) procedure as well as complete revalidation as needed. Your firm expects to complete this activity by September 30, 2015.
The response is not adequate because although your firm stated that it will review all existing process validation documents by September 30, 2015, your firm has not indicated whether it would review all manufacturing processes requiring validation to ensure that they are appropriately validated. Your firm has not provided evidence of implementation of a correction to include defining and documenting the acceptance criteria for (b)(4). In addition, your firm has not provided a statistical rationale for choosing a sampling size (b)(4). Your firm has not indicated if the revised work instructions for the (b)(4) would include the sample size to be tested based on a statistical rationale to address this deficiency. Your firm has not provided evidence that employees will be trained on the revised validation work instructions for (b)(4).
2. Failure to establish and maintain procedures for monitoring and control of process parameters for validated processes to ensure that the specified requirements continue to be met, as required by 21 CFR 820.75(b). For example, your firm has not established procedures for the monitoring of process parameters for processes such as (b)(4) used in the manufacturing of the Urisys 1100 device. Your firm did not establish procedures which identify the data to be monitored, control limits, or how the data generated from the monitoring of the validated processes are to be reviewed and analyzed. During the inspection, Mr. Rudolf Tolgyesi, QA Director, indicated that your firm did not have any procedures that identified what data was required to be collected and evaluated and the control limits for (b)(4).
We reviewed your firm’s response and conclude that it is not adequate. Your firm states that although (b)(4) does not specify monitoring and control of process parameters for validated processes to ensure that specified requirements continue to be met, your firm has validated the production process of Urisys 1100 and the Urisys 1100 analyzers undergo 100% functional testing and non-conformities during production process are trended. Your firm has undertaken the following corrections and corrective actions:
i. Opened CAPA 2015-036 for this observation.
ii. Plans to revise (b)(4) add requirements for monitoring and control of process parameters for validated processes. Your firm plans to complete the revision by April 30, 2015.
iii. Plans to define and document monitoring and control of process parameters for (b)(4) based on the revised (b)(4) Procedure by September 30, 2015 and conduct effectiveness checks by October 9, 2015.
iv. Plans to review all validated processes and define and document monitoring and control of all validated process parameters in accordance with revised (b)(4) by September 30, 2015 and conduct effectiveness checks by October 9, 2015.
The response is not adequate because your firm did not provide evidence that a systemic corrective action was considered to include a retrospective review of all processes to ensure that appropriate monitoring and control of process parameters occurs as required. Your firm has not defined the monitoring procedure for the (b)(4). In addition, your firm has not provided evidence that employees have been trained on the revised procedures.
3. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example:
a. Your firm did not evaluate and select suppliers based on the supplier’s ability to meet specified requirements, including quality requirements. Your firm did not evaluate and document the supplier of LEDs used in the manufacture of Urisys 1100. In addition, the questionnaire used for selection of several suppliers as well as the semi-annual evaluation did not include any field for supplier quality requirements. During the inspection, the investigator requested documentation on critical supplier selection, and your firm was unable to provide documentation for LED supplier, a critical component of the Urisys 1100 analyzer. Mr. Rudolf Tolgyesi, your firm’s QA Director, stated that your firm has been using the LED supplier for a long time and had not had any issues.
b. Your firm did not define the type and extent of control to be exercised over the product and suppliers based on the evaluation. Mr. Rudolf Tolgyesi, your firm's QA Director, stated your firm is aware of non-conformances associated with a critical component (Motor for Urisys 1100) from the supplier for over three years. Your firm continues to receive the same component from the same supplier. During production, your firm (b)(4) nonconforming component.
We reviewed your firm’s response and conclude that it is not adequateYour firm states that during supplier selection, it evaluates if suppliers are ISO9001 and/or ISO13485 certified, and your firm asks quality related questions if the suppliers are not. Your firm has undertaken the following corrections and corrective actions:
i. Opened CAPA 2015-034 for part of this observation and CAPA 2015-035 for part b of this observation.
ii. Plans to re-evaluate LED supplier by April 15, 2015.
iii. Plans to update the supplier selection procedure and modify, if needed, to meet the requirements of 21 CFR 820.50. The estimated date for completion of this activity is May 30, 2015.
iv. Plans to evaluate supplier according to revised procedure for the first half of 2015 to determine which of the current suppliers exceed the control limits. The estimated date for completion of this activity is July 31, 2015.
v. Plans to define the type and extent of control, i.e., the actions to be applied if a supplier is above the control limits in the half-year evaluation. The work instructions will be updated to include the standardized rules. Your firm expects to complete this activity by August 31, 2015.
vi. Plans to review and revise (b)(4) based on 21 CFR 820.50 requirements to include appropriate statistical techniques for sampling plan.
vii. Plans to define control limits for the production non-conformity and quality control by June 5, 2015.
Your firm did not provide evidence that it plans to implement corrective actions to include quality requirements in its supplier evaluations as required, and that the products meet specified requirements. Your firm did not provide a valid rationale for selecting the six-month timeframe for the review of supplier evaluation. Your firm did not provide evidence of consideration of a systemic corrective action including a retrospective review of all suppliers to ensure that all specified purchasing control requirement were being met. Your firm also did not provide evidence that personnel are trained on the revised procedures.
4. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198(a). For example, your firm's complaint procedure “Complaint Handling and Servicing” procedure, (b)(4), do not require the complete Device History Record (DHR) for a medical device to be reviewed upon receiving a complaint on the product. Your firm (b)(4) nonconforming components e.g, the motor of Urisys 1100 analyzers prior to their release and distribution. The in-process nonconformance is documented on the DHR. Mr. Rudolf Tolgyesi, QA Director, stated that your firm does not review the complete DHR for information which may be attributed to the failure of the device.
We reviewed your firm’s response and conclude that it is not adequate. Your firm opened CAPA 2015-032 for this observation. Your firm has undertaken the following corrections and corrective actions:
i. Your firm plans to update the (b)(4) Complaint Handling and Servicing Procedure to add DHR review requirements by April 30, 2015.
ii. Your firm plans to review the DHR for retrospective investigation of the complaint information of returned instruments received (b)(4) from Jan 2014 to present. The expected date of completion for this activity is September 30, 2015.
The response is not adequate because your firm has not provided evidence of consideration of a systemic corrective action to include reviewing the entire complaint handling subsystem to ensure that all sources of errors are evaluated and all requirements for complaint handling are being met. Also, your firm has not provided a justification for limiting the review of complaints from January 2014 to April 2015. Your firm did not provide evidence to demonstrate that employees are trained on the revised procedures.
U.S. federal agencies may be advised of the issuance of Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket approval applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to correct the noted violations, including an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective action (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.
Your firm’s response should be sent to: Food and Drug Administration, Center for Devices and Radiological Health, Office of Compliance, Field Inspections Support Branch, White Oak Building 66, Rm 2622, 10903 New Hampshire Ave., Silver Spring, MD 20993. Refer to CMS case # 458367 when replying. If you have any questions about the contents of this letter, please contact: James L. Woods, at 301-796-625 or 301-847-8513 (fax).
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.
Office of In Vitro Diagnostics and
Center for Devices and